Bendamustine Hydrochloride and Rituximab With or Without Bortezomib Followed by Rituximab With or Without Lenalidomide in Treating Patients With High-Risk Stage II, Stage III, or Stage IV Follicular Lymphoma

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Effect of continuation therapy in converting partial response or stable disease from induction into CR

Association of the original FLIPI-1 score with the recently reported FLIPI-2 score

Relationship between FLIPI-2 score and outcome

Overall health-related quality of life and disease-related symptoms as assessed by the FACT-Lymphoma subscale (FACTLym)

Treatment-related symptoms as assessed by the 13-item FACT-Fatigue scale and the 11-item FACT/GOG-Neurotoxicity scale

Disease-related symptoms and distress as assessed by the patient self-report assessment

Number of co-morbidities as assessed by the Cumulative Illness Rating Scale (CIRS) at 2 years

Relationship between CIRS score and outcome

Original Secondary Outcome Measures ICMJE

Same as current

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

Bendamustine Hydrochloride and Rituximab With or Without Bortezomib Followed by Rituximab With or Without Lenalidomide in Treating Patients With High-Risk Stage II, Stage III, or Stage IV Follicular Lymphoma

Official Title ICMJE

A 3-Arm Randomized Phase II Trial of Bendamustine-Rituximab (BR) Followed by Rituximab vs Bortezomib-BR (BVR) Followed by Rituximab vs BR Followed by Lenalidomide/Rituximab in High Risk Follicular Lymphoma

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving bendamustine hydrochloride and rituximab together alone is more effective than giving bendamustine hydrochloride and rituximab together with bortezomib or lenalidomide in treating follicular lymphoma.

PURPOSE: This randomized phase II trial is studying giving bendamustine hydrochloride and rituximab together with or without bortezomib followed by rituximab with or without lenalidomide to see how well they work in treating patients with high-risk stage II, stage III, or stage IV follicular lymphoma.

Arm I: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Beginning 4 weeks after the completion of induction therapy, patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Arm II: Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Beginning 4 weeks after the completion of induction therapy, patients receive rituximab as in arm I.

Arm III: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Immediately after completing induction therapy, patients receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Quality of life (including fatigue, neurotoxicity, anxiety, and depression) is assessed by questionnaire at baseline and periodically during study therapy.

Blood, bone marrow, and tissue samples may be collected periodically for correlative studies and for a repository.

After completion of study therapy, patients are followed up periodically for 15 years.

Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Interventions:

Biological: rituximab

Drug: bendamustine hydrochloride

Experimental: Arm II

Patients receive rituximab IV on day 1, bortezomib IV on days 1, 4, 8, and 11, and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab as in arm I.

Interventions:

Biological: rituximab

Drug: bendamustine hydrochloride

Drug: bortezomib

Experimental: Arm III

Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Immediately after completing induction therapy, patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Interventions:

Biological: rituximab

Drug: bendamustine hydrochloride

Drug: lenalidomide

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Histologically confirmed (biopsy-proven) diagnosis of follicular B-cell non-Hodgkin lymphoma with no evidence of transformation to large cell histology

Patients having both diffuse and follicular architectural elements are eligible if the histology is predominantly follicular (i.e., ≥ 50% of the cross-sectional area) and there is no evidence of transformation to a large cell histology

Must meet criteria for High Tumor Burden (higher risk) as defined by either the Groupe D'Etude des Lymphomes Follicularies (GELF) criteria OR the follicular lymphoma international prognostic index (FLIPI) as defined below:

No history of CD4 < 300 cells/mm³ prior to or at the time of lymphoma diagnosis

No history of AIDS-defining conditions

If on antiretroviral therapy, must not be taking zidovudine or stavudine

Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia (PCP) during therapy and ≥ 2 months following completion of study therapy or until the CD4 cells recover to over 250 cells/mm³

No recent history of malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for ≥ 2 years

Patients with a prior history of HBV infection, but immune, with only IgG hepatitis core antibody positive (HBcAb+), must receive antiviral prophylaxis (e.g., lamivudine 100 mg po daily) for ≥ 1 week prior to course 1 and throughout induction and continuation therapy and for ≥ 12 months after the last rituximab dose

Must register into the mandatory RevAssist® program and be willing and able to comply with the requirements of RevAssist® (for patients randomized to arm III)

PRIOR CONCURRENT THERAPY:

No prior chemotherapy, radiotherapy, or immunotherapy for lymphoma

Prednisone or other corticosteroids used for non-lymphomatous conditions will not be considered as prior chemotherapy

A prior/recent short course (< 2 weeks) of steroids for symptom relief of lymphoma-related symptoms is allowed

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years to 120 Years (Adult, Senior)

Accepts Healthy Volunteers

No

Contacts ICMJE

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